- Direct18F-Labeling of Biomolecules via Spontaneous Site-Specific Nucleophilic Substitution by F-on Phosphonate Prostheses
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We describe a high radiochemical yield late-stage direct 18F-labeling of bare biomolecules containing common active groups. Spontaneity and site-selectivity are attributed to the remarkably higher rates of nucleophilic substitution reactions on phosphonates than on other electrophiles by F- at various hydrogen bond forms. Rapid access to many medicinally significant 18F-labeled biomolecules is achieved at 21-68% radiochemical yields and 35.9-55.1 GBq μmol-1 molar activities both manually or automatically.
- Wang, Chao,Zhang, Lei,Mou, Zhaobiao,Feng, Wanru,Li, Zhongjing,Yang, Hongzhang,Chen, Xueyuan,Lv, Shengji,Li, Zijing
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supporting information
p. 4261 - 4266
(2021/05/26)
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- METHOD FOR PRODUCING ORGANOPHOSPHORUS COMPOUND
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PROBLEM TO BE SOLVED: To provide a method for producing an organophosphorus compound which has excellent energy efficiency without containing a halogenated alkyl or a by-product derived from a halogenated alkyl. SOLUTION: There is provided a method for producing an organophosphorus compound by reacting a trivalent organophosphorus compound represented by the following general formula (1) in the presence of a super strong acid and/or at least one acid catalyst containing a solid superstrong acid catalyst to generate a pentavalent organophosphorus compound represented by the following general formula. (where Z1 represents OR2 or R2; Z2 represents OR3 or R3; R1, R2 and R3 represent an alkyl group, an alkenyl group or the like; when R2 and R3 are an alkyl group or the like, R2 and R3 may be bonded to each other to form a cyclic structure; and R1 may be a hydrogen atom.) SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
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Paragraph 0052; 0079
(2020/05/02)
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- Water determines the products: An unexpected Br?nsted acid-catalyzed PO-R cleavage of P(iii) esters selectively producing P(O)-H and P(O)-R compounds
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Water is found able to determine the selectivity of Br?nsted acid-catalyzed C-O cleavage reactions of trialkyl phosphites: with water, the reaction quickly takes place at room temperature to afford quantitative yields of H-phosphonates; without water, the reaction selectively affords alkylphosphonates in high yields, providing a novel halide-free alternative to the famous Michaelis-Arbuzov reaction. This method is general as it can be readily extended to phosphonites and phosphinites and a large scale reaction with much lower loading of the catalyst, enabling a simple, efficient, and practical preparation of the corresponding organophosphorus compounds. Experimental findings in control reactions and substrate extension as well as preliminary theoretical calculation of the possible transition states all suggest that the monomolecular mechanism is preferred.
- Li, Chunya,Wang, Qi,Zhang, Jian-Qiu,Ye, Jingjing,Xie, Ju,Xu, Qing,Han, Li-Biao
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supporting information
p. 2916 - 2922
(2019/06/18)
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- NRF2 REGULATORS
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Provided are aryl analogs,pharmaceutical compositions containing them and their use as NRF2 regulators.
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Page/Page column 269; 270
(2017/01/02)
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- DBU-promoted alkylation of alkyl phosphinates and H-phosphonates
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The alkylation of alkyl phosphinates and some H-phosphonate diesters is promoted by the base DBU. Only more reactive alkyl halides react in preparatively useful yields. However, the method provides easy access to important H-phosphinate building blocks, without the need for a protecting group strategy or metal catalysts. The reaction is conveniently conducted at, or below, room temperature. The preparation of methyl-H-phosphinate esters is particularly interesting as it avoids the heretofore more common use of methyldichlorophosphine MePCl2.
- Gavara, Laurent,Petit, Christelle,Montchamp, Jean-Luc
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supporting information
p. 5000 - 5003
(2012/11/07)
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- DIARYL ALKYLPHOSPHONATES AND METHODS FOR PREPARING SAME
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A method for preparing substantially pure optionally substituted diaryl alkylphosphonates from an optionally substituted triarylphosphite and an optionally substituted trialkylphosphite or an optionally substituted alkanol under special reaction conditions is described.
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Page/Page column 7
(2009/08/18)
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- Mechanistic study of Protein Phosphatase-1 (PP1), a catalytically promiscuous enzyme
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The reaction catalyzed by the protein phosphatase-1 (PP1) has been examined by linear free energy relationships and kinetic isotope effects. With the substrate 4-nitrophenyl phosphate (4NPP), the reaction exhibits a bell-shaped pH-rate profile for kcat/KM indicative of catalysis by both acidic and basic residues, with kinetic pKa values of 6.0 and 7.2. The enzymatic hydrolysis of a series of aryl monoester substrates yields a Bronsted βlg of -0.32, considerably less negative than that of the uncatalyzed hydrolysis of monoester dianions (-1.23). Kinetic isotope effects in the leaving group with the substrate 4NPP are 18(V/K)bridge = 1.0170 and 15(V/K) = 1.0010, which, compared against other enzymatic KIEs with and without general acid catalysis, are consistent with a loose transition state with partial neutralization of the leaving group. PP1 also efficiently catalyzes the hydrolysis of 4-nitrophenyl methylphosphonate (4NPMP). The enzymatic hydrolysis of a series of aryl methylphosphonate substrates yields a Bronsted βlg of -0.30, smaller than the alkaline hydrolysis (-0.69) and similar to the βlg measured for monoester substrates, indicative of similar transition states. The KIEs and the βlg data point to a transition state for the alkaline hydrolysis of 4NPMP that is similar to that of diesters with the same leaving group. For the enzymatic reaction of 4NPMP, the KIEs are indicative of a transition state that is somewhat looser than the alkaline hydrolysis reaction and similar to the PP1-catalyzed monoester reaction. The data cumulatively point to enzymatic transition states for aryl phosphate monoester and aryl methylphosphonate hydrolysis reactions that are much more similar to one another than the nonenzymatic hydrolysis reactions of the two substrates.
- McWhirter, Claire,Lund, Elizabeth A.,Tanifum, Eric A.,Feng, Guoqiang,Sheikh, Qaiser I.,Hengge, Alvan C.,Williams, Nicholas H.
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experimental part
p. 13673 - 13682
(2009/02/06)
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- DIARYL ALKYLPHOSPHONATES AND METHODS FOR PREPARING SAME
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A method of making optionally substituted diaryl alkylphosphonates from an optionally substituted arylol, an optionally substituted alkanol, and a phosphorous trihalide is described.
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Page/Page column 5
(2008/06/13)
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- DIARYL ALKYLPHOSPHONATES AND METHODS FOR PREPARING SAME
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A method for preparing substantially pure optionally substituted diaryl alkylphosphonates from an optionally substituted triarylphosphite and an optionally substituted trialkylphosphite or an optionally substituted alkanol under special reaction conditions is described.
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Page/Page column 25-26
(2010/11/28)
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- An efficient method for the esterification of phosphonic and phosphoric acids using silica chloride
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Silica chloride is used as an effective heterogeneous catalyst for the rapid esterification of alkyl/aryl phosphonic/phosphoric acids to their corresponding alkyl/aryl phosphonates/phosphates under mild conditions with quantitative yields.
- Sathe, Manisha,Gupta, Arvind K.,Kaushik
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p. 3107 - 3109
(2007/10/03)
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- Surface-mediated solid phase reactions: A simple, efficient and base-free synthesis of phosphonates and phosphates on Al2O3
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Al2O3-supported solvent free condensation of alkylphosphonic dichlorides with alcohols at room temperature yielded phosphorus esters in excellent yields.
- Acharya, Jyotiranjan,Shakya, Purushottam D.,Pardasani, Deepak,Palit, Meehir,Dubey, Devendra K.,Gupta, Arvind K.
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p. 194 - 196
(2007/10/03)
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- Total synthesis of microtubule-stabilizing agent (-)-laulimalide
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An enantioselective first total synthesis of laulimalide (1) is described. Laulimalide, a remarkably potent antitumor macrolide, has been isolated from the Indonesian sponge Hyattella sp. and the Okinawan sponge Fasciospongia rimosa. Laulimalide represents a new class of antitumor agents with significant clinical potential. The synthesis is convergent and involved the assembly of C3-C16 segment 4 and C17-C28 segment 5 by Julia olefination. The sensitive C2-C3 cis-olefin functionality was installed by Yamaguchi macrolactonization of a hydroxy alkynic acid followed by hydrogenation of the resulting alkynoic lactone over Lindlar's catalyst. Initial attempts of intramolecular Still's variant of Horner - Emmons olefination between the C19-phosphonocetate and C3-aldehyde provided a 1:2 mixture of cis- and trans-macrolactones. The trans-isomer was photo-isomerized to a mixture of cis- and trans-isomers. The other key steps involved ring-closing olefin metathesis to construct both dihydropyran units, stereoselective anomeric alkylation to functionalize the dihydropyran ring, stereoselective reduction of the resulting alkynyl ketone to set the C20-hydroxyl stereochemistry, and a novel Julia olefination protocol for the installation of the C13-exomethylene unit. The sensitive epoxide at C16-C17 was introduced in a highly stereoselective manner by Sharpless epoxidation at the final stage of the synthesis.
- Ghosh,Wang,Kim
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p. 8973 - 8982
(2007/10/03)
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- One pot synthesis of diastereomeric phosphonates
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The reaction of diaryl methylphosphonate with sterically hindered alcohols in presence of sodium hydride provide arylalkyl methylphosphonate esters with high diastereoselectivity at the phosphorus center.
- Saxena, Shefali,Sharma, Mamta,Purnanand
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p. 259 - 266
(2007/10/03)
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- Reductive cleavage of the halogen-phosphorus, oxygen-phosphorus and phosphorus-phosphorus bonds with alkali metals
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The reduction of phosphorus acid chlorides as well as hypophosphates, pyrophosphates and mixed P(III)-P(V) anhydrides with alkali metals (Li, Na, K) in NH3 liq. / THF solution and potassium naphthalenide was investigated. It was found that this type of phosphorus compounds easily undergo reduction: a) >P(O)Cl to >P(O)H; b) >P(O)P(O)P(O)H; c) >P(O)-O-P(O)P(O)OH and >P(O)H; d) >P(O)-O-PP(O)O- and >P-. The results of our experiments strongly suggest that the mixed P(III)-P(V) anhydride is reduced by potassium naphthalenide in THF with the cleavage of the P(III)-oxygen bond.
- Nycz, Jacek,Rachon, Janusz
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- New feature of Friedel-Crafts phosphonation of anisoles: Unexpected in situ methylphosphorylation reaction
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Anisoles 1, reacting with AlCl3 and PCl3 with appropriate reagent ratios, give, in good yields, the corresponding diaryl methylphosphonates 2 or the methylphoshinates 3b,c and the methylphosphine oxides 4b,c. This unexpected in situ methylphosphorylation explains the reported limited and conflicting results to obtain methoxy-substituted arylphosphonous dichloride with the same reagents. A suggested mechanism is also reported.
- Baccolini, Graziano,Boga, Carla
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p. 822 - 824
(2007/10/03)
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- An efficient and practical synthesis of diphenyl cyanomethylenephosphonate: Applications to the stereoselective synthesis of cis-α,β-unsaturated nitriles
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Diphenyl cyanomethylenephosphonate (PhO)2POCH2CN was prepared as a stable crystalline solid in high yield in a single step from acetonitrile, LDA, and (PhO)2P(O)CI. The potassium ylide generated from this compound afforded α,β-unsaturated nitriles upon reacting with aldehydes, with a stereoselectivity of 64-100% favoring the cis-isomer.
- Zhang, Tony Y.,O'Toole, John C.,Dunigan, James M.
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p. 1461 - 1464
(2007/10/03)
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- Diphenyl methylphosphonate as a phosphonylation reagent with high diastereoselectivity at phosphorus
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Reaction of diphenyl methylphosphonate with lithium alkoxides generated in situ from alcohols and butyllithium gives phenyl alkyl methylphosphonate diesters even with hindered alcohols and with high diastereoselectivity at phosphorus.
- Moriarty, Robert M.,Tao, Anping,Condeiu, Cristian,Gilardi, Richard
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p. 2597 - 2600
(2007/10/03)
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- PHOTOLYSIS OF ARYL ESTERS OF TRI- AND TETRACOORDINATED PHOSPHORUS COMPOUNDS
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Upon UV excitation in methanol, some diaryl esters of alkly- or alkenyl phosphonates underwent an elimination of two aryl groups to give biaryls and the corresponding alkyl- or alkenylphosphonic acids.Tris(4-methoxyphenyl) phosphite also underwent a similar elimination to give 4,4'-dimethoxybiphenyl and 4-methoxyphenyl phosphonate.This interesting biaryl elimination was confirmed to proceed via a singlet intramolecular excimer by means of fluorescence spectra and Stern-Volmer analysis.
- Shi, Min,Yamamoto, Kiichi,Okamoto, Yoshiki,Takamuku, Setsuo
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- Quasiphosphonium Intermediates. Part 3. Preparation, Structure, and Reactivity of Alkoxyphosphonium Halides in the Reaction of Neopentyl Diphenylphosphinite, Dineopentyl Phenylphosphinite, and Trineopentyl Phosphite with Halogenomethanes and the Effect of Phenoxy-substituenst on the ...
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The reactions of neopenthyl diphenylphosphinite with chloro-, bromo-, or iodo-methane and of dineopentyl phenylphosphphonite with bromo- or iodo-methane yield crystalline alkoxyphosphonium halides.In deuteriochloroform these intermediates decompose by a first-order process which involves rate-determining collapse of the phosphonium halide ion-pair with SN2-type fission of the alkyl-oxygen bond.Rates for chloride, bromide, and iodide are similar.In a more ionising medium (deuterioacetonitrile) dissociation leads to stabilisation of the intermediates and to deviation from first-order decomposition.Previously determined X-ray diffraction data for the bromides, together with relative rates of decomposition in deuteriochloroform for intermediates in the series Phn(RO)3-nP+MeX- (n = 0,1, or 2) suggest that the stability and reactivity of alkoxyphosphonium intermediates are determined largely by inductive rather than mesomeric effects of ligands.The presence of phenoxy-substituents on phosphorus may cause a tendency towards SN1-type fission of the alkyl-oxygen bond in certain circumstances.
- Hudson, Harry R.,Kow, Aloysius,Roberts, John C.
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p. 1363 - 1368
(2007/10/02)
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- Alkoxyphosphonium Salts. 3. Kinetics and Thermodynamics in Alkylation by Alkoxyphosphonium Salts
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Several methoxyphosphonium trifluoromethanesulfonates (triflates) are characterized by the rates of methyl transfer to the 2,4-dinitrophenoxide ion.In acetone at 25 deg C, the measured second-order rate constants range from about 0.2 to about 40 M-1s-1, putting substances of this class among the most powerful methylating agents.The methylating power is confirmed by the measurement of the equilibrium extent of methylation of the counterion, the triflate ion.The Arbuzov rearrangement of trimethyl phosphite is slow with the catalyst methyl iodide but is fast enough with the cata lyst methyltrimethoxyphosphonium triflate to allow calorimetric measurement for the conversion of trimethyl phosphite to dimethyl methylphosphonate; ΔH = -24 +/- 2 kcal/mol.An earlier error in the measurement of the rate of this reaction is corrected, so that the mechanism of the methyl iodide catalyzed Arbuzov reaction of trimethyl phosphite is no longer in question; the first step is rate-determining.
- Lewis, Edward S.,Colle, Karla S.
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p. 4369 - 4372
(2007/10/02)
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- Process for preparing diaryl methylphosphonate and derivatives thereof
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A process is provided for the preparation of diaryl methylphosphonates through the reaction of triaryl phosphites with methanol in the presence of a catalytic quantity of methyl iodide. The reaction is conducted at a temperature of from about 170° C. to about 250° C. New and useful derivatives are produced by reaction of the diaryl methylphosphonates with polyols or amines.
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- Scrambling of substituents between dimethylsilicon and various methylphosphorus moieties
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Equilibrium constants have been measured for the scrambling of pairs of substituents between the (CH3)2Si3P3P(O)3P(S)a phenoxyl or dimethylamino group, the chlorine is preferentially bonded to the silicon in the case of the CH3P(O)3P(S)3P moiety. The quantitative equilibrium data are discussed, as are the kinetics of exchange of chlorine and bromine between the dimethylsilicon and the methylthiophosphonyl moieties.
- Moedritzer, Kurt,Van Wazer, John R.
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p. 2856 - 2859
(2007/10/05)
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